chr6-31543147-A-G

Position:

• chr6-31543147-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000376185.5(ATP6V1G2-DDX39B):​n.184-999T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,142 control chromosomes in the GnomAD database, including 4,425 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (4425 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: ATP6V1G2-DDX39B ENST00000376185.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64

Genes affected

ATP6V1G2-DDX39B (HGNC:41999): (ATP6V1G2-DDX39B readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring ATP6V1G2 (ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G2) and DDX39B (DEAD box polypeptide 39B) genes located in the major histocompatibility complex class III region of chromosome 6. The read-through transcript and is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ATP6V1G2-DDX39B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP6V1G2-DDX39B	NR_037853.1	n.473-999T>C		intron_variant
DDX39B-AS1	NR_133674.1	n.*9A>G		downstream_gene_variant
DDX39B-AS1	NR_133675.1	n.*9A>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP6V1G2-DDX39B	ENST00000376185.5	n.184-999T>C		intron_variant		2		ENSP00000365356.1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35083 AN: 152000 Hom.: 4426 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.269

GnomAD4 exome AF: 0.167 AC: 4 AN: 24 Hom.: 0 Cov.: 0 AF XY: 0.0625 AC XY: 1 AN XY: 16

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.125

GnomAD4 genome AF: 0.231 AC: 35124 AN: 152118 Hom.: 4425 Cov.: 32 AF XY: 0.228 AC XY: 16969 AN XY: 74384

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.271

Alfa AF: 0.261 Hom.: 6770

Bravo AF: 0.249

Asia WGS AF: 0.199 AC: 691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2844509; hg19: chr6-31510924;